Spinal disc annulus reconstruction method and spinal disc annulus stent

ABSTRACT

A surgical method of repair and reconstruction of the spinal disc wall (annulus) after surgical invasion or pathologic rupture, incorporating suture closure, or stent insertion and fixation, designed to reduce the failure rate of conventional surgical procedures on the spinal discs. The design of the spinal disc annulus stent allows ingrowth of normal cells of healing in an enhanced fashion strengthening the normal reparative process.

CROSS-REFERENCE TO A RELATED APPLICATION

This application is a continuation of U.S. Ser. No. 09/947,078, filedSep. 5, 2001, now U.S. Pat. No. 6,592,625; which is a continuation ofU.S. Ser. No. 09/484,706, filed Jan. 18, 2000, (now abandoned); whichclaims the benefit of U.S. Provisional Application No. 60/160,710, filedOct. 20, 1999.

FIELD OF THE INVENTION

The invention generally relates to a surgical method of intervertebraldisc wall reconstruction. The invention also relates to an annularrepair device, or stent, for annular disc repair. The effects of saidreconstruction are restoration of disc wall integrity and reduction ofthe failure rate (3–21%) of a common surgical procedure (disc fragmentremoval or discectomy). This surgical procedure is performed about390,000 times annually in the United States.

BACKGROUND OF THE INVENTION

The spinal column is formed from a number of vertebrae, which in theirnormal state are separated from each other by cartilaginousintervertebral discs. The intervertebral disc acts in the spine as acrucial stabilizer, and as a mechanism for force distribution betweenthe vertebral bodies. Without the disc, collapse of the intervertebralspace occurs in conjunction with abnormal joint mechanics and prematuredevelopment of arthritic changes.

The normal intervertebral disc has an outer ligamentous ring called theannulus surrounding the nucleus pulposus. The annulus binds the adjacentvertebrae together and is constituted of collagen fibers that areattached to the vertebrae and cross each other so that half of theindividual fibers will tighten as the vertebrae are rotated in eitherdirection, thus resisting twisting or torsional motion. The nucleuspulposus is constituted of loose tissue, having about 85% water content,which moves about during bending from front to back and from side toside.

The aging process contributes to gradual changes in the intervertebraldiscs. The annulus loses much of its flexibility and resilience,becoming more dense and solid in composition. The aging annulus is alsomarked by the appearance on propagation of cracks or fissures in theannular wall. Similarly, the nucleus dessicates, increasing viscosityand thus losing its fluidity. In combination, these features of the agedintervertebral discs result in less dynamic stress distribution becauseof the more viscous nucleus pulposus, and less ability to withstandlocalized stresses by the annulus fibrosus due to its dessication, lossof flexibility and the presence of fissures. Occasionally fissures mayform rents through the annular wall. In these instances, the nucleuspulposus is urged outwardly from the subannular space through a rent,often into the spinal column. Extruded nucleus pulposus can, and oftendoes, mechanically press on the spinal cord or spinal nerve rootlet.This painful condition is clinically referred to as a ruptured orherniated disc.

In the event of annulus rupture, the subannular nucleus pulposusmigrates along the path of least resistance forcing the fissure to openfurther, allowing migration of the nucleus pulposus through the wall ofthe disc, with resultant nerve compression and leakage of chemicals ofinflammation into the space around the adjacent nerve roots supplyingthe extremities, bladder, bowel and genitalia. The usual effect of nervecompression and inflammation is intolerable back or neck pain, radiatinginto the extremities, with accompanying numbness, weakness, and in latestages, paralysis and muscle atrophy, and/or bladder and bowelincontinence. Additionally, injury, disease or other degenerativedisorders may cause one or more of the intervertebral discs to shrink,collapse, deteriorate or become displaced, herniated, or otherwisedamaged and compromised.

The surgical standard of care for treatment of herniated, displaced orruptured intervertebral discs is fragment removal and nervedecompression without a requirement to reconstruct the annular wall.While results are currently acceptable, they are not optimal. Variousauthors report 3.1–21% recurrent disc herniation, representing a failureof the primary procedure and requiring re-operation for the samecondition. An estimated 10% recurrence rate results in 39,000re-operations in the United States each year.

An additional method of relieving the symptoms is thermal annuloplasty,involving the heating of sub-annular zones in the non-herniated painfuldisc, seeking pain relief, but making no claim of reconstruction of theruptured, discontinuous annulus wall.

There is currently no known method of annulus reconstruction, eitherprimarily or augmented with an annulus stent.

BRIEF SUMMARY OF THE INVENTION

The present invention provides methods and related materials forreconstruction of the disc wall in cases of displaced, herniated,ruptured, or otherwise damaged intervertebral discs. In accordance withthe invention, an annulus stent is disclosed for repair of anintervertebral disc annulus, comprising a centralized hub section, saidhub section comprising lateral extensions from the hub section.

In an exemplary embodiment, one or more mild biodegradable surgicalsutures are placed at about equal distances along the sides of apathologic aperture in the ruptured disc wall (annulus) or along thesides of a surgical incision in the annular wall, which may be weakenedor thinned.

Sutures are then tied in such fashion as to draw together the sides ofthe aperture, effecting reapproximation or closure of the opening, toenhance natural healing and subsequent reconstruction by natural tissue(fibroblasts) crossing the now surgically narrowed gap in the discannulus.

A 25–30% reduction in the rate of recurrence of disc nucleus herniationthrough this aperture, has been achieved using this method.

In another embodiment as depicted in FIG. 7B, the method can beaugmented by creating a subannular barrier in and across the aperture byplacement of a patch of human muscle fascia (the membrane covering themuscle) or any other autograft, allograft, or xenograft acting as abridge or a scaffold, providing a platform for traverse of fibroblastsor other normal cells of repair existing in and around the variouslayers of the disc annulus, prior to closure of the aperture.

A 30–50% reduction in the rate of recurrence of disc herniation has beenachieved using the aforementioned fascial augmentation with thisembodiment.

Having demonstrated that human muscle fascia is adaptable for annularreconstruction, other blocompatible membranes can be employed as abridge, stent, patch or barrier to subsequent migration of the discnucleus through the aperture. Such biocompatible materials may be, forexample, medical grade biocompatible fabrics, biodegradable polymericsheets, or form fitting or non-form fitting fillers for the cavitycreated by removal of a portion of the disc nucleus pulposus in thecourse of the disc fragment removal or discectomy. The prostheticmaterial can be placed in and around the intervertebral space, createdby removal of the degenerated disc fragments.

Additional objects and advantages of the invention will be set forth inpart in the description which follows, and in part will be obvious fromthe description, or may be learned by practice of the invention. Theobjects and advantages of the invention will be realized and attained bymeans of the elements and combinations particularly pointed out in theappended claims.

It is to be understood that both the foregoing general description andthe following detailed description are exemplary and explanatory onlyand are not restrictive of the invention, as claimed.

BRIEF DESCRIPTION OF THE DRAWINGS

The accompanying drawings, which are incorporated in and constitute apart of this specification, illustrate illustrative embodiments of theinvention and, together with the description, serve to explain theprinciples of the invention.

FIG. 1 shows a perspective view of an illustrative embodiment of anannulus stent.

FIG. 2 shows a front view of the annulus stent of FIG. 1.

FIG. 3 shows a side view of the annulus stent of FIG. 1.

FIGS. 4A–4C show a front view of alternative illustrative embodiments ofan annulus stent.

FIGS. 5A–5B show the alternative embodiment of a further illustrativeembodiment of an annulus stent.

FIGS. 6A–6B show the alternative embodiment of a further illustrativeembodiment of an annulus stent.

FIGS. 7A–7B show a primary closure of an opening in the disc annulus.

FIGS. 8A–8B show a primary closure with a stent.

FIG. 9 shows a method of suturing an annulus stent into the discannulus, utilizing sub-annular fixation points.

FIGS. 10A–10B show a further illustrative embodiment of an annulus stentwith flexible bladder being expanded into the disc annulus.

FIGS. 11A–11D show an annulus stent being inserted into the discannulus.

FIGS. 12A–12B show an annulus stent with a flexible bladder beingexpanded.

Reference will now be made in detail to an illustrative embodiment ofthe invention, which appears in the accompanying drawings. Whereverpossible, the same reference numbers will be used throughout thedrawings to refer to the same or like parts.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides methods and related materials forreconstruction of the disk wall in cases of displaced, herniated,ruptured, or otherwise damaged intervertebral discs.

In one embodiment of the present invention, as shown in FIG. 7A, adamaged annulus 42 is repaired by use of surgical sutures 40. One ormore surgical sutures 40 are placed at about equal distances along thesides of a pathologic aperture 44 in the annulus 42. Reapproximation orclosure of the aperture 44 is accomplished by tying the sutures 40 sothat the sides of the aperture 44 are drawn together. Thereapproximation or closure of the aperture 44 enhances the naturalhealing and subsequent reconstruction by the natural tissue (e.g.,fibroblasts) crossing the now surgically narrowed gap in the annulus 42.Preferably, the surgical sutures 40 are biodegradable, but permanentnon-biodegradable may be utilized.

Additionally, to repair a weakened or thinned wall of a disc annulus 42,a surgical incision is made along the weakened or thinned region of theannulus 42 and one or more surgical sutures 40 can be placed at aboutequal distances laterally from the incision. Reapproximation or closureof the incision is accomplished by tying the sutures 40 so that thesides of the incision are drawn together. The reapproximation or closureof the incision enhances the natural healing and subsequentreconstruction by the natural tissue crossing the now surgicallynarrowed gap in the annulus 42. Preferably, the surgical sutures 40 arebiodegradable, but permanent non-biodegradable materials may beutilized.

In an alternative embodiment as depicted in FIG. 7B, the method can beaugmented by the placement of a patch of human muscle fascia or anyother autograft, allograft or xenograft in and across the aperture 44.The patch acts as a bridge in and across the aperture 44, providing aplatform for traverse of fibroblasts or other normal cells of repairexisting in and around the various layers of the disc annulus 42, priorto closure of the aperture 44.

In a further embodiment, as shown in FIGS. 8A–B a biocompatible membranecan be employed as an annulus stent 10, being placed in and across theaperture 44. The annulus stent 10 acts as a bridge in and across theaperture 44, providing a platform for a traverse of fibroblasts or othernormal cells of repair existing in and around the various layers of thedisc annulus 42, prior to closure of the aperture 44.

In an illustrative embodiment, as shown in FIGS. 1–3, the annulus stent10 comprises a centralized vertical extension 12, with an upper section14 and a lower section 16. The centralized vertical extension 12 can betrapezoid in shape through the width and may be from about 8 mm–12 mm inlength.

Additionally, the upper section 14 of the centralized vertical extension12 may be any number of different shapes, as shown in FIGS. 4A and 4B,with the sides of the upper section 14 being curved or with the uppersection 14 being circular in shape. Furthermore, the annulus stent 10may contain a recess between the upper section 14 and the lower section16, enabling the annulus stent 10 to form a compatible fit with theedges of the aperture 44.

The upper section 14 of the centralized vertical extension 12 cancomprise a slot 18, where the slot 18 forms an orifice through the uppersection 14. The slot 18 is positioned within the upper section 14 suchthat it traverses the upper section's 14 longitudinal axis. The slot 18is of such a size and shape that sutures, tension bands, staples or anyother type of fixation device known in the art may be passed through, toaffix the annulus stent 10 to the disc annulus 42.

In an alternative embodiment, the upper section 14 of the centralizedvertical extension 12 may be perforated. The perforated upper section 14contains a plurality of holes that traverse the longitudinal axis ofupper section 14. The perforations are of such a size and shape thatsutures, tension bands, staples or any other type of fixation deviceknown the art may be passed through, to affix the annulus stent 10 tothe disc annulus 42.

The lower section 16 of the centralized vertical extension 12 cancomprise a pair of lateral extensions, a left lateral extension 20 and aright lateral extension 22. The lateral extensions 20 and 22 comprise aninside edge 24, an outside edge 26, an upper surface 28, and a lowersurface 30. The lateral extensions 20 and 22 can have an essentiallyconstant thickness throughout. The inside edge 24 is attached to and isabout the same length as the lower section 16. The outside edge 26 canbe about 8 mm–16 mm in length. The inside edge 24 and the lower section16 meet to form a horizontal plane, essentially perpendicular to thecentralized vertical extension 12. The upper surface 28 of the lateralextensions 20 and 22 can form an angle from about 0°–60° below thehorizontal plane. The width of the annulus stent 10 may be from about 3mm–5 mm.

Additionally, the upper surface 28 of the lateral extensions 20 and 22may be barbed for fixation to the inside surface of the disc annulus 42and to resist expulsion through the aperture 44.

In an alternative embodiment, as shown in FIG. 4B, the lateralextensions 20 and 22 have a greater thickness at the inside edge 24 thanat the outside edge 26.

In an illustrative embodiment, the annulus stent 10 is a solid unit,formed from one or more of the flexible resilient biocompatible orbioresorbable materials well know in the art.

For example, the annulus stent 10 may be made from:

-   -   a porous matrix of mesh of biocompatible and bioresorbable        fibers acting as a scaffold to regenerate disc tissue and        replace annulus fibrosus as disclosed in, for example, U.S. Pat.        No. 5,108,438 (Stone) and U.S. Pat. No. 5,258,043 (Stone), a        strong network of inert fibers intermingled with a bioresorbable        (or bioabsorbable) material which attracts tissue ingrowth as        disclosed in, for example, U.S. Pat. No. 4,904,260 (Ray et al.);    -   a biodegradable substrate as disclosed in, for example, U.S.        Pat. No. 5,964,807 (Gan et al.); or    -   an expandable polytetrafluoroethylene (ePTFE), as used for        conventional vascular grafts, such as those sold by W. L. Gore        and Associates, Inc. under the trademarks GORE-TEX and PRECLUDE,        or by Impra, Inc. under the trademark IMPRA.

Furthermore, the annulus stent 10, may contain hygroscopic material fora controlled limited expansion of the annulus stent 10 to fill theevacuated disc space cavity.

Additionally, the annulus stent 10 may comprise materials to facilitateregeneration of disc tissue, such as bioactive silica-based materialsthat assist in regeneration of disc tissue as disclosed in U.S. Pat. No.5,849,331 (Ducheyne, et al.), or other tissue growth factors well knownin the art.

In further embodiments, as shown in FIGS. 5AB–6AB, the left and rightlateral extensions 20 and 22 join to form a solid pyramid or cone.Additionally, the left and right lateral extensions 20 and 22 may form asolid trapezoid, wedge, or bullet shape. The solid formation may be asolid biocompatible or bioresorbable flexible material, allowing thelateral extensions 20 and 22 to be compressed for insertion intoaperture 44, then to expand conforming to the shape of the annulus' 42inner wall.

Alternatively, a compressible core may be attached to the lower surface30 of the lateral extensions 20 and 22, forming a pyramid, cone,trapezoid, wedge, or bullet shape. The compressible core may be madefrom one of the biocompatible or bioresorbable resilient foams wellknown in the art. The core can also comprise a fluid-expandablemembrane, e.g., a balloon. The compressible core allows the lateralextensions 20 and 22 to be compressed for insertion into aperture 44,then to expand conforming to the shape of the annulus' 42 inner wall andto the cavity created by pathologic extrusion or surgical removal of thedisc fragment.

In an illustrative method of use, as shown in FIGS. 11A–D, the lateralextensions 20 and 22 are compressed together for insertion into theaperture 44 of the disc annulus 42. The annulus stent 10 is theninserted into the aperture 44, where the lateral extensions 20, 22expand. In an expanded configuration, the upper surface 28 cansubstantially conform to the contour of the inside surface of the discannulus 42. The upper section 14 is positioned within the aperture 44 sothat the annulus stent 10 may be secured to the disc annulus 42, usingmeans well known in the art.

In an alternative method, where the length of the aperture 44 is lessthan the length of the outside edge 26 of the annulus stent 10, theannulus stent 10 can be inserted laterally into the aperture 44. Thelateral extensions 20 and 22 are compressed, and the annulus stent 10can then be laterally inserted into the aperture 44. The annulus stent10 can then be rotated inside the disc annulus 42, such that the uppersection 14 can be held back through the aperture 44. The lateralextensions 20 and 22 are then allowed to expand, with the upper surface28 contouring to the inside surface of the disc annulus 42. The uppersection 14 can be positioned within, or proximate to, the aperture 44 inthe subannular space such that the annulus stent 10 may be secured tothe disc annulus, using means well known in the art.

In an alternative method of securing the annulus stent 10 in theaperture 44, as shown in FIG. 9, a first surgical screw 50 and secondsurgical screw 52, with eyeholes 53 located at the top of the screws 50and 52, are opposingly inserted into the adjacent vertebrae 54 and 56below the annulus stent 10. After insertion of the annulus stent 10 intothe aperture 44, a suture 40 is passed down through the disc annulus 42,adjacent to the aperture 44, through the eye hole 43 on the first screw50 then back up through the disc annulus 42 and through the orifice 18on the annulus stent 10. This is repeated for the second screw 52, afterwhich the suture 40 is secured. One or more surgical sutures 40 areplaced at about equal distances along the sides of the aperture 44 inthe disc annulus 42. Reapproximation or closure of the aperture 44 isaccomplished by tying the sutures 40 in such a fashion that the sides ofthe aperture 44 are drawn together. The reapproximation or closure ofthe aperture 44 enhances the natural healing and subsequentreconstruction by the natural tissue crossing the now surgicallynarrowed gap in the annulus 42. Preferably, the surgical sutures 40 arebiodegradable but permanent non-biodegradable forms may be utilized.This method should decrease the strain on the disc annulus 42 adjacentto the aperture 44, precluding the tearing of the sutures through thedisc annulus 42.

It is anticipated that fibroblasts will engage the fibers of the polymeror fabric of the intervertebral disc stent 10, forming a strong wallduplicating the currently existing condition of healing seen in thenormal reparative process.

In an additional embodiment, as shown in FIGS. 10A–B, a flexible bladder60 is attached to the lower surface 30 of the annulus stent 10. Theflexible bladder 60 comprises an internal cavity 62 surrounded by amembrane 64, where the membrane 64 is made from a thin flexiblebiocompatible material. The flexible bladder 60 is attached to the lowersurface 30 of the annulus stent 10 in an unexpanded condition. Theflexible bladder 60 is expanded by injecting a biocompatible fluid orexpansive foam, as known in the art, into the internal cavity 62. Theexact size of the flexible bladder 60 can be varied for differentindividuals. The typical size of an adult nucleus is about 2 cm in thesemi-minor axis, 4 cm in the semi-major axis, and 1.2 cm in thickness.

In an alternative embodiment, the membrane 64 is made of asemi-permeable biocompatible material.

In an illustrative embodiment, a hydrogel is injected into the internalcavity 62 of the flexible bladder 60. A hydrogel is a substance formedwhen an organic polymer (natural or synthetic) is cross-linked via,covalent, ionic, or hydrogen bonds to create a three-dimensionalopen-lattice structure, which entraps water molecules to form a gel. Thehydrogel may be used in either the hydrated or dehydrated form.

In a method of use, where the annulus stent 10 has been inserted intothe aperture 44, as has been previously described and shown in FIGS.12A–B, an injection instrument, as known in the art, such as a syringe,is used to inject the biocompatible fluid or expansive foam into theinternal cavity 62 of the flexible bladder 60. The biocompatible fluidor expansive foam is injected through the annulus stent 10 into theinternal cavity 62 of the flexible bladder 60. Sufficient material isinjected into the internal cavity 62 to expand the flexible bladder 60to fill the void in the intervertebral disc cavity. The use of theflexible bladder 60 is particularly useful when it is required to removeall or part of the intervertebral disc nucleus.

The surgical repair of an intervertebral disc may require the removal ofthe entire disc nucleus, being replaced with an implant, or the removalof a portion of the disc nucleus thereby leaving a void in theintervertebral disc cavity. The flexible bladder 60 allows for theremoval of only the damaged section of the disc nucleus, with theexpanded flexible bladder 60 filling the resultant void in theintervertebral disc cavity. A major advantage of the annulus stent 10with the flexible bladder 60 is that the incision area in the annulus 42can be reduced in size, as there is no need for the insertion of animplant into the intervertebral disc cavity.

In an alternative method of use, a dehydrated hydrogel is injected intothe internal cavity 62 of the flexible bladder 60. Fluid, from the discnucleus, passes through the semipermeable membrane 64 hydrating thedehydrated hydrogel. As the hydrogel absorbs the fluid the flexiblebladder 60 expands, filling the void in the intervertebral disc cavity.

All patents referred to or cited herein are incorporated by reference intheir entirety to the extent they are not inconsistent with the explicitteachings of this specification, including; U.S. Pat. No. 5,108,438(Stone), U.S. Pat. No. 5,258,043 (Stone), U.S. Pat. No. 4,904,260 (Rayet al.), U.S. Pat. No. 5,964,807 (Gan et al.), U.S. Pat. No. 5,849,331(Ducheyne et al.), U.S. Pat. No. 5,122,154 (Rhodes), U.S. Pat. No.5,204,106 (Schepers at al.), U.S. Pat. No. 5,888,220 (Felt et al.)andU.S. Pat. No. 5,376,120 (Sarver et al.).

It should be understood that the examples and embodiments describedherein are for illustrative purposes only and that various modificationsor changes in light thereof will be suggested to persons skilled in theart and are to be included within the spirit and preview of thisapplication and the scope of the appended claims.

1. A method for treating an intervertebral disc having an aperture inthe annulus fibrosus, wherein the aperture provides a pathway for themigration of intradiscal material from the subannular space, the methodcomprising the steps of: inserting a hinged device through the aperturein a first collapsed configuration and causing or allowing the device toexpand into a second configuration within the subannular space wherebysaid device at least partially spans said aperture, thereby resistingthe migration of intradiscal material through the aperture.
 2. Themethod of claim 1 wherein the device is comprised at least in part of ashape memory material.
 3. The method of claim 1, wherein the device iscomprised at least in part of a biocompatible material.
 4. The method ofclaim 3, wherein said device is comprised at least in part from abiocompatible membrane.
 5. The method of claim 3, wherein said device iscomprised at least in part from a biocompatible fabric.
 6. The method ofclaim 3, wherein the device is comprised at least in part from abiocompatible mesh.
 7. The method of claim 6, wherein the biocompatiblemesh is a fibrous mesh.
 8. The method of claim 3, wherein the device iscomprised at least in part from a biocompatible sheet.
 9. The method ofclaim 1, wherein the device is at least in part bioabsorbable.
 10. Themethod of claim 1, further comprising the step of treating the annulustissue surrounding the aperture to reduce the relative motion thereof.11. The method of claim 10, further comprising the step ofreapproximating the aperture.
 12. The method of claim 11, wherein thedevice further comprises at least one element for reapproximating theaperture.
 13. The method of claim 1, wherein the device furthercomprises at least one fixation element for attaching the device to theannulus.
 14. The method of claim 1, wherein the aperture is pathologic.15. The method of claim 1, wherein the aperture is formed at least inpart by a surgical incision.
 16. A method for treating an intervertebraldisc having an aperture in the annulus fibrosus, wherein the method ofclaim 1 is performed following discectomy.
 17. The method of claim 1,further comprising the step of applying sutures to acutely stabilizesaid device.
 18. The method of claim 1, wherein said device is comprisedat least in part from a polymeric material.
 19. The method of claim 18,wherein the device is comprised at least in part from a polymeric sheet.20. The method of claim 18, wherein the device is comprised at least inpart from a polymeric fabric.
 21. The method of claim 18, wherein thedevice is comprised at least in part from a polymeric mesh.
 22. Themethod of claim 18, wherein the device is comprised at least in partfrom polymeric fibers.
 23. The method of claim 1, wherein said device isapplied at least in part in said aperture.
 24. The method of claim 23,wherein said device comprises a filler material.
 25. The method of claim24, wherein said filler is at least in part form-fitting.
 26. The methodof claim 24, wherein said filler is at least in part non-form-fitting.27. The method of claim 1, further comprising the step of placingsutures at about equal distances along the sides of the aperture. 28.The method of claim 1, wherein at least a portion of the devicecomprises a biodegradable or bioresorbable material.
 29. The method ofclaim 28, wherein the biodegradable or bioresorbable material comprisesa mesh.
 30. The method of claim 28, wherein the biodegradable materialcomprises a sheet.
 31. The method of claim 1, wherein the device iscomprised of a material selected from the group consisting of expandablepolytetrafluoroethylene (ePTFE), a material to facilitate regenerationof disc tissue, and a hygroscopic material.
 32. The method of claim 31,wherein the material to facilitate tissue growth comprises a bioactivesilica based material.
 33. The method of claim 31, wherein the materialto facilitate tissue growth comprises a growth factor.
 34. The method ofclaim 1, wherein at least a portion of the device is porous.
 35. Themethod of claim 1, wherein at least a portion of the device isnon-porous.